Suspected of being hazardous to humans since the 1930s, concerns
about the use of bisphenol A in consumer products were regularly
reported in the news media in 2008 after several governments issued
reports questioning its safety, and some retailers have removed
products made of it from their shelves.

A large number of ketones undergo analogous condensation reactions.
The method is efficient and the only by-product is water.

Use

Repeating chemical structure unit of
polycarbonate made from bisphenol A

Bisphenol A is used primarily to make plastics, and products
containing bisphenol A-based plastics have been in commerce for
more than 50 years. It is used in the synthesis of polyesters, polysulfones, and polyetherketones, as an
antioxidant in some plasticizers, and as a polymerization inhibitor in PVC. It is a key monomer in production of epoxy
resins and in the most common form of polycarbonateplastic.
Polycarbonate plastic, which is clear and nearly shatter-proof, is
used to make a variety of common products including baby and water
bottles, sports equipment, medical and dental devices, dental fillings and sealants, eyeglass
lenses, CDs and DVDs, and household electronics. Epoxy resins
containing bisphenol A are used as coatings on the inside of almost
all food and beverage cans. Bisphenol A is also a precursor to the
flame retardant, tetrabromobisphenol A, and was
formerly used as a fungicide.

Identification in plastics

There are seven
classes of plastics used in packaging applications. Type 7 is
the catch-all "other" class, and some type 7 plastics, such as
polycarbonate (sometimes identified
with the letters "PC" near the recycling symbol) and epoxy resins, are
made from bisphenol A monomer.

Type 3 (PVC) can also contain bisphenol A as an
antioxidant in plasticizers.

Health effects

Bisphenol A is an endocrine
disruptor, which can mimic the body's own hormones and may lead to negative health effects.
Early development appears to be the period of greatest sensitivity
to its effects. Regulatory bodies have determined safety levels for
humans, but those safety levels are currently being questioned as a
result of new scientific studies. The European Food Safety
Authority (EFSA) TDI (Tolerable Daily Intake) of 0.05mg (50µg)
/kg/day is orders of magnitude greater than the dose found to
produce effects in some rodent studies. (see table below) The EFSA
notion that rodent toxicity data are not directly relevant to human
risk assessment is also being questioned.

In 2009 the The Endocrine
Society released a scientific statement expressing concern over
current human exposure to BPA.

Previous studies

In 2007, a consensus statement by 38 experts on bisphenol A
concluded that average levels in people are above those that cause
harm to animals in laboratory experiments. A panel convened by the
U.S. National Institutes of Health determined that there was "some concern" about
BPA's effects on fetal and infant brain development and
behavior. A 2008 report by the U.S. National Toxicology Program
(NTP) later agreed with the panel, expressing "some concern for
effects on the brain, behavior, and prostate gland in fetuses,
infants, and children at current human exposures to bisphenol A,"
and "minimal concern for effects on the mammary gland and an
earlier age for puberty for females in fetuses, infants, and
children at current human exposures to bisphenol A." The NTP had
"negligible concern that exposure of pregnant women to bisphenol A
will result in fetal or neonatal mortality, birth defects, or
reduced birth weight and growth in their offspring."

Obesity

A 2008 review has concluded that obesity may be increased as a
function of BPA exposure, which "merits concern among scientists
and public health officials". A 2009 review of available studies
has concluded that "perinatal BPA exposure acts to exert persistent
effects on body weight and adiposity". Another 2009 review has
concluded that "Eliminating exposures to (BPA) and improving
nutrition during development offer the potential for reducing
obesity and associated diseases". Other reviews have come with
similar conclusions. A later study on mice has shown that perinatal
exposure to drinking water containing 1 mg/L of BPA increased
adipogenesis in females at weaning.

Breast cancer

A 2008 review has concluded that "perinatal exposure to (...) low
doses of (..) BPA, alters breast development and increases breast
cancer risk". Another 2008 review concluded that " animal
experiments and epidemiological data strengthen the hypothesis that
foetal exposure to xenoestrogens may be an underlying cause of the
increased incidence of breast cancer observed over the last 50
years". A 2009 review, funded by the "Breast Cancer Fund", has
recommended "a federal ban on the manufacture, distribution and
sale of consumer products containing bisphenol A".

A 2009 study has concluded that BPA is able to induce neoplastic
transformation in human breast epithelial cells.

Neurological issues

A panel convened by the U.S. National Institutes of Health determined that there was "some concern" about
BPA's effects on fetal and infant brain development and
behavior. A 2008 report by the U.S. National Toxicology Program
(NTP) later agreed with the panel, expressing "some concern for
effects on the brain".

A 2007 review has concluded that BPA, like other xenoestrogens,
should be considered as a player within the nervous system that can
regulate or alter its functions through multiple pathways. A 2007
review has concluded that low doses of BPA during development have
persistent effects on brain structure, function and behavior in
rats and mice. A 2008 review concluded that low-dose BPA maternal
exposure causes long-term consequences at the level of
neurobehavioral development in mice. A 2008 review has concluded
that neonatal exposure to Bisphenol-A (BPA) can affect sexually
dimorphic brain morphology and neuronal phenotypes in adulthood. A
2008 review has concluded that BPA altered long-term potentiation in the
hippocampus and even nanomolar dosage
could induce significant effects on memory processes. A 2009 review
raised concerns about BPA effect on anteroventral
periventricular nucleus.

A 2005 review concluded that prenatal and neonatal exposure to BPA
can potentiate the central dopaminergic systems, resulting in the
supersensitivity of the drugs of abuse-induced rewarding effects
and hyperlocomotion in the mouse.

A 2009 study on rats has concluded that prenatal and neonatal
exposure to low-dose BPA causes deficits in development at
dorsolateral striatum via altering the
function of dopaminergic receptors.

Thyroid function

A 2007 review has concluded that bisphenol-A have been shown to
bind to thyroid hormone receptor and perhaps have selective effects
on its functions.

A 2009 review about environmental chemicals and thyroid function,
raised concerns about BPA effects on triiodothyronine and concluded that
"available evidence suggests that governing agencies need to
regulate the use of thyroid-disrupting chemicals, particularly as
such uses relate exposures of pregnant women, neonates and small
children to the agents".

BPA exposure disrupted the blood-testis barrier when administered
to immature, but not to adult, rats.

Exposure to BPA in the workplace could produce sexual
dysfunction in male adult humans.

Prostate development and cancer

A 1997 study in mice has found that neonatal BPA exposure of 2
μg/kg increased adult prostate weight. A 2005 study in mice has
found that neonatal BPA exposure at 10 μg/kg disrupted the
development of the fetal mouse prostate.A 2006 study in rats has
shown that neonatal bisphenol A exposure at 10 μg/kg levels
increases prostate gland susceptibility to adult-onset precancerous
lesions and hormonal carcinogenesis.A 2007 in vitro study has found
that BPA within the range of concentrations currently measured in
human serum is associated with permanently increase in prostate
size. A 2009 study has found that newborns rats exposed to a
low-dose of BPA (10 µg/kg) increased prostate cancer susceptibility
when adults.

Neuroblastoma

In vitro studies have suggested that BPA can promote the growth of
neuroblastoma cells.

General research

In 2009, at an Endocrine Society
meeting new research reported data from animals experimentally
treated with BPA. Studies presented at the group's annual meeting
show BPA can affect the hearts of women, can permanently damage the
DNA of mice, and appear to be entering the human body from a
variety of unknown sources.

Studies on humans

Lang study

The first major study of health effects on humans associated with
bisphenol A exposure was published in September 2008 by Iain Lang
and colleagues in the Journal of the
American Medical Association. The cross-sectional study of
almost 1,500 people assessed exposure to bisphenol A by looking at
levels of the chemical in urine. The authors found that higher
bisphenol A levels were significantly associated with
heart disease, diabetes, and abnormally high levels of certain
liver enzymes. An editorial in the same issue notes that while this
preliminary study needs to be confirmed and cannot prove causality,
there is precedent for analogous effects in animal studies, which
"add[s] biological plausibility to the results reported by Lang et
al."

Historical studies

The first evidence of the estrogenicity of bisphenol A came from
experiments on rats conducted in the 1930s, but it was not until
1997 that adverse effects of low-dose exposure on laboratory
animals were first reported.

Different expression of ERR-γ in different parts of the body may
account for variations in bisphenol A effects. For instance, ERR-γ
has been found in high concentration in the placenta, explaining reports of high bisphenol A
accumulation in this tissue.

Human exposure sources

Bisphenol A has been known to leach from the plastic lining of
canned foods and, to a lesser degree, polycarbonate plastics, especially those that are cleaned with
harsh detergents or used to contain acidic or high-temperature
liquids. A recent Health Canada study found that the majority of
canned soft drinks it tested had low, but
measurable levels of bisphenol A. This exposure through metal cans
is due to the fact that BPA is an ingredient in the internal
coating of food and beverage metal cans used to protect the food
from direct contact with metal. While most human exposure is
through diet, exposure can also occur through air and through skin
absorption.

Studies by the CDC found
bisphenol A in the urine of 95% of adults sampled in 1988–1994 and
in 93% of children and adults tested in 2003–04. Infants fed with
liquid formula are among the most exposed, and those fed formula
from polycarbonate bottles can consume up to 13 micrograms of
bisphenol A per kg of body weight per day (μg/kg/day; see table
below). The most sensitive animal studies show effects at much
lower doses, while the EPA considers exposures up to
50 µg/kg/day to be safe. In 2009, a study found that drinking
from polycarbonate bottles increased urinary bisphenol A levels by
two thirds, from 1.2 micrograms/gram creatinine to 2
micrograms/gram creatinine.

Consumer groups recommend that people wishing to lower their
exposure to bisphenol A avoid canned food and polycarbonate plastic
containers (which shares resin
identification code 7 with many other plastics) unless the
packaging indicates the plastic is bisphenol A-free. The National
Toxicology Panel recommends avoiding microwaving food in plastic
containers, putting plastics in the dishwasher, or using harsh
detergents, to avoid leaching.

Population

Estimated daily bisphenol A intake, μg/kg/day.

Table adapted from the National Toxicology Program Expert Panel
Report.

Infant (0–6 months)

formula-fed

1–11

Infant (0–6 months)

breast-fed

0.2–1

Infant (6–12 months)

1.65–13

Child (1.5–6 years)

0.043–14.7

Adult

0.008–1.5

Pharmacokinetics

There's no agreement between scientists of a PBPK BPA
model for humans. BPA effects in a organism depends of how much
free BPA is available and for how long cells are exposed to it.
Glucuronidation in the organism
reduces the amount of free BPA, however BPA glucuronide can be
deconjugated by beta-glucuronidase, an enzyme present in high
concentration in placenta and other tissues. Free BPA can also be
inactivated by sulfation, a process that can also be reverted by
arysulfatase C.

A 2009 review of the biological impacts of plasticizers on wildlife
published by the Royal Society with a
focus on annelids (both aquatic and terrestrial), molluscs, crustaceans,
insects, fish and amphibians concluded
that BPA have been shown to affect reproduction in all studied
animal groups, to impair development in crustaceans and amphibians
and to induce genetic aberrations.

Government and industry response

Australia and New Zealand

The Australia and New Zealand Food Safety Authority (Food Standards Australia
New Zealand) does not see any health risk with bisphenol A
baby bottles if the manufacturers
instructions are followed. Levels of exposure are very low and do
not pose a significant health risk. It added that “the move by
overseas manufacturers to stop using BPA in baby bottles is a
voluntary action and not the result of a specific action by
regulators.”[87132] It suggests the use of glass baby
bottles if parents have any concerns.

Canada

In April 2008, Health Canada assessed
that the chemical may pose some risk to infants and proposed
classifying the chemical as "'toxic' to human health and the
environment."

After the release of that assessment, Canadian Health Minister
Tony Clement announced Canada's intent
to ban the import, sale, and advertisement of polycarbonate baby
bottles containing bisphenol A due to safety concerns, and
investigate ways to reduce BPA contamination of baby formula
packaged in metal cans. While the agency concluded that human
exposures were less than levels believed to be unsafe, the margin
of safety was not high enough for formula-fed infants. Around the same time,
Wal-Mart announced
that it was immediately ceasing sales in all its Canadian stores of
food containers, water and baby bottles, sippy cups, and pacifiers
containing bisphenol A, and that it would phase out baby bottles
made with it in U.S. stores by early 2009.Nalgene also announced it will stop using the
chemical in its products, and Toys-R-Us
said it too will cease selling baby bottles made from it.
Subsequent news reports showed many retailers removing
polycarbonate drinking products from their shelves.

In 2006, Canadian regulators selected bisphenol A as one of 200
substances deserving of thorough safety assessments because
preliminary studies had found it to be "inherently toxic"; the
chemical had not previously been studied by them in depth, having
been accepted under grandfather
clauses when stricter regulations were passed in the
1980s.

The federal government has formally declared bisphenol A a
hazardous substance as of October 2008 and is now placed on its
list of toxic substances. Health officials wrote in Canada Gazette that "It is concluded
that bisphenol A be considered as a substance that may be entering
the environment in a quantity or concentration or under conditions
that constitute or may constitute a danger in Canada to human life
or health." The federal ministries of health and the environment announced they would seek to
restrict imports, sales and advertising of polycarbonate baby bottles containing
BPA.

In its statement Gc.ca released on 18 October 2008, Health
Canada noted that “bisphenol A exposure to newborns and infants is
below levels that cause effects” and that the “general public need
not be concerned”.

Europe

European Union

The updated 2008 European Union Risk Assessment Report on bisphenol
A, published in June 2008 by the European Commission concluded that
bisphenol A-based products, such as polycarbonate plastic and epoxy
resins, are safe for consumers and the environment when used as
intended.

On 24 October 2008, European Food Safety Authority (EFSA) issued a
statement following the Lang Study concluding that the study
provided no grounds to revise the current TDI (Tolerable Daily
Intake) level for BPA of 0.05 mg/kg bodyweight.

On 2009 a scientific study criticized the European risk assessment
processes of endocrine disruptors, including BPA.

Denmark

In May 2009, the Danish parliament passed a resolution to ban the
use of BPA in baby bottles.

France

On 24 October 2008, a French Food Safety Agency (AFSSA) literature
review concluded that the heating of polycarbonate baby bottles on
microwave, in realistic conditions (less than 10 minutes), was safe
as by EFSA's maximum TDI.

Later, in March 2009, the French health minister Mrs. Roselyne
Bachelot-Narquin agreed with the AFSSA conclusion evaluating that
“The Canadian authorities decided on the ban on BPA (baby bottles)
as a result of public pressure not on the basis of valid scientific
studies.”

On 27 July 2009, French senator members of the RDSE proposed legislation to ban BPA of plastics used
as food containers.

On 16 October 2009 the French Food Safety Agency (AFSSA) announced
it would reevaluate BPA safety.

Germany

On 19 September 2008, the German Federal Institute for Risk
Assessment (Bundesinstitut für Risikobewertung, BfR) stated that
there was no reason to change the current risk assessment for
bisphenol A on the basis of the Lang Study.

On October 2009, the German environmental organization Bund für Umwelt
und Naturschutz Deutschland requested a ban on BPA for children
products, specially pacifiers, and
products that make contact with food. In response some manufactures
voluntary removed the problematic pacifiers from the market.

Netherlands

On 6 November 2008, the Dutch Food and Consumer Product Safety
Authority (VWA), stated in a newsletter that baby bottles made from
polycarbonate plastic do not release measurable concentrations of
bisphenol A and therefore are safe to use.

Switzerland

In February 2009 the Swiss Federal Office for Public Health, based
on reports of other health agencies, stated that the intake of
bisphenol A from food represents no risk to the consumer, including
newborns and infants. However, in the same statement it advised for
proper use of polycarbonate baby bottles and listed
alternatives.

United States

April 2008

As of the
release of NTP and Health Canada reports in April, 10 U.S. states,
including California, Maryland, and
New
Jersey, already had legislation pending that would affect
the use of BPA. In the wake of these reports, U.S.SenatorCharles Schumer (D–N.Y.) introduced
legislation that would ban bisphenol A nationally from products for
infants. In addition, the U.S. Congress is investigating the
Weinberg Group, a chemical industry
consulting firm, for its role in downplaying the health effects of
bisphenol A and other chemicals, and the Energy and Commerce Committee
in the House of
Representatives is investigating the use of BPA in baby
products as well as the FDA's approval of the chemical.
In asking
the FDA to reassess its approval of bisphenol A, committee chairman
Bart Stupak (D–Mich.) said "We
would expect the FDA to make decisions based on the best available
science…Yet the FDA relied on only two industry-funded studies,
while other respected authorities used all available data to reach
vastly different conclusions." The FDA maintained that
bisphenol A is safe and did not recommend that people avoid using
products made from it. The Consumer Product Safety
Commission agreed, and its deputy director stressed that use of
bisphenol A based plastics has many practical benefits and that "a
ban could result in less effective protection of children from
head, eye, or bodily injury." FDA then announced it would set up a
task force to address these concerns, and in August it released a
draft finding concurring with its initial position that the
chemical is safe. The agency will make its final decision after an
advisory panel on the issues is convened in September.

In response to these events, an American Chemistry Council
(ACC)/BPA Global Group (an industry trade association) spokesman
said, “The weight of scientific evidence, as assessed by Health
Canada and other agencies around the world, provides reassurance
that consumers can continue to safely use products made from
bisphenol A." The Grocery Manufacturers
Association also insisted that bisphenol A is safe, and argues
that "Data purporting to demonstrate 'low' dose effects on the male
reproductive system by BPA have not been successfully replicated
and, therefore, are not credible to estimate human health risks and
safety in light of the weight of a large body of evidence to the
contrary." A spokesman for the tin can
industry said that without lining cans with bisphenol A based
resins, E. coli and botulism
poisoning would be "rampant."

September 2008

In September, the National Toxicology Program finalized their
report on bisphenol A, finding "some concern", mid-point of a
five-level scale, that infants were at risk from exposure to the
chemical.

At that time, the FDA reassured consumers that current limits were
safe, but convened an outside panel of experts to review the issue.
The Lang study was also
released that month, and David Melzer, a co-author of the study,
presented the results of the study before the FDA panel.

The editorial accompanying the Lang study's publication in
JAMA criticized the FDA's assessment of bisphenol A: "A
fundamental problem is that the current ADI [acceptable daily
intake] for BPA is based on experiments conducted in the early
1980s using outdated methods (only very high doses were tested) and
insensitive assays. More recent findings from independent
scientists were rejected by the FDA, apparently because those
investigators did not follow the outdated testing guidelines for
environmental chemicals, whereas studies using the outdated,
insensitive assays (predominantly involving studies funded by the
chemical industry) are given more weight in arriving at the
conclusion that BPA is not harmful at current exposure
levels."

The Union of Concerned
Scientists similarly criticized the agency saying, "We're
concerned that the FDA is basing its conclusion on two studies
while downplaying the results of hundreds of other studies.... This
appears to be a case of cherry-picking data with potentially high
cost to human health." Diana
Zuckerman, president of the National
Research Center for Women and Families, also criticized the
FDA, saying, in her testimony at the FDA's public meeting on the
draft assessment of bisphenol A for use in food contact
applications, that "At the very least, the FDA should require a
prominent warning on products made with BPA".

In contrast, the American Chemistry Council, the manufacturing
industry's lobby group, was skeptical of the latest study.

March 2009

Sunoco, a producer of gasoline and chemicals, is now refusing to
sell the chemical to companies for use in food and water containers
for children younger than 3, saying it can't be certain of the
compound's safety. Sunoco plans to require its customers to
guarantee that the chemical will not be used in children's food
products.

The six largest US companies which commercialize baby bottles
decided to stop using bisphenol A in their products.Suffolk County, New York banned baby beverage
containers made with bisphenol A.

On March 13 leaders from the House and Senate proposed legislation
to ban bisphenol A.

In the same month, Rochelle Tyl, author of two studies used by FDA
to assert BPA safety in August 2008, said those studies didn't
claim that BPA is safe since they weren't designed to cover all
aspects of the chemical's effects.

May 2009

Among the
first states to pass regulations limiting or banning BPA were
Minnesota and Illinois.
Minnesota's regulation takes effect in 2010, "manufacturers of ...
children's products containing BPA may not sell them in the state
after Jan. 1, 2010. The ban extends to all retailers in the state a
year later." The products impacted are known as sippy cups and baby
bottles. The City of Chicago adopted a similar ban shortly
thereafter. Coverage of Chicago's ban in the news showed a
relentless opposition by the industry. A Chicago Tribune article
noted an up-hill battle while passing legislation, "[industry
officials] used FDA’s position on the issue when they tried to
block the city’s measure." It further notes that,

“The FDA continues to be recalcitrant and very slow about taking
any action on BPA,” said Ald. Manny Flores (1st), who co-sponsored
the Chicago measure with Ald. Edward Burke.

Chicago bans the sale after 2010 of any empty food or drink
container containing BPA that is intended for use by children less
than 3 years old.

Burke and Flores pushed the measure through after backing down from
a more aggressive version that would have outlawed nearly any
product for children that was made with the chemical. Still, the
chemical industry fought hard to thwart the scaled-back ban,
including hiring former Ald. Terry Gabinski to lobby against it.
The American Chemistry Council trade group responded with a written
statement that called [the] vote “unwarranted.”.

In May 2009 the Washington Post accused the manufacturers of food
and beverage containers and some of their biggest customers of
trying to devise a public relations and lobbying strategy to block
government BPA bans.

June 2009

In June 2009, the FDA announced the decision to reconsider the BPA
safety levels.

Connecticut was the first US state to ban bisphenol A from
infant formula and baby food containers, as well from any reusable
food or beverage container.

July 2009

The California Environmental Protection Agency's Developmental and
Reproductive Toxicant Identification Committee unanimously voted
against placing Bisphenol A on the state's list of chemicals that
are believed to cause reproductive harm. The panel, although
concerned over the growing scientific research showing BPA's
reproductive harm in animals, found that there was insufficient
data of the effects in humans. Critics point out that the same
panel failed to add second-hand
smoke to the list until 2006, and only one chemical was added
to the list in the last three years.

August 2009

On August 3, Massachusetts' Department of Public Health advised
mothers to take certain actions to prevent possible health impact
in children. Mothers with children up to two years old were advised
to limit exposure by avoiding products that might contain BPA, such
as plastic drinking bottles and other plastic materials with
recycling
codes of 7 or 3.

The Milwaukee Journal
Sentinel, as part of an ongoing investigative series into
BPA and its effects, revealed plans by the Society of the Plastics
Industry to execute a major public relations blitz to promote
BPA, including plans to attack and discredit those who report or
comment negatively on the monomer and its effects.

September 2009

November 2009

The Consumer Reports magazine
published a analysis of BPA content in some canned foods and
beverages, where in specific cases the content of a single can of
food could exceed the current FDA Cumulative Exposure Daily
Intake.

This table is adapted from: EWG, 2007. "Many studies confirm
BPA's low-dose toxicity across a diverse range of toxic effects,"
Environmental Working Group Report: A Survey of Bisphenol A in U.S.
Canned Foods. Accessed November 4th, 2007 at
http://www.ewg.org/node/20941. All studies included in this table
where judged by the CEHRH panel to be at least of moderate
usefulness for assessing the risk of BPA to human
reproduction.